DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Kim, Ho Min | - |
dc.contributor.advisor | 김호민 | - |
dc.contributor.author | Kim, Hyojin | - |
dc.date.accessioned | 2023-06-23T19:33:19Z | - |
dc.date.available | 2023-06-23T19:33:19Z | - |
dc.date.issued | 2023 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=1030509&flag=dissertation | en_US |
dc.identifier.uri | http://hdl.handle.net/10203/309035 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 의과학대학원, 2023.2,[iv, 83 p. :] | - |
dc.description.abstract | Insulin-like growth factors (IGFs) have pleiotropic roles in embryonic and postnatal growth and differentiation. Most serum IGFs are bound in a ternary complex with IGF-binding protein 3 (IGFBP3) and acid-labile subunit (ALS), extending the serum half-life of IGFs and regulating their availability. Here, we report cryo-EM structure of the human IGF1/IGFBP3/ALS ternary complex, revealing the detailed architecture of a parachute-like ternary complex and crucial determinants for their sequential and specific assembly. In vitro biochemical studies show that proteolysis at the central linker domain of IGFBP3 induces release of its C-terminal domain rather than IGF1 release from the ternary complex, yielding an intermediate complex that enhances IGF1 bioavailability. Our results provide mechanistic insight into IGF/IGFBP3/ALS ternary complex assembly and its disassembly upon proteolysis for IGF bioavailability, suggesting a structural basis for human diseases associated with IGF1 and IGFALS gene mutations such as complete ALS deficiency (ACLSD) and IGF1 deficiency. | - |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | IGF▼aIGFBP▼aALS▼aProtein structure▼aCryo-EM | - |
dc.subject | IGF▼aIGFBP▼aALS▼a단백질 구조▼a초저온 투과전자현미경 | - |
dc.title | Structural basis for assembly and disassembly of the IGF/IGFBP/ALS ternary complex | - |
dc.title.alternative | IGF/IGFBP/ALS ternary complex의 분자기전에 대한 구조연구 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 325007 | - |
dc.description.department | 한국과학기술원 :의과학대학원, | - |
dc.contributor.alternativeauthor | 김효진 | - |
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